SN-38

SN-38

Names
Preferred IUPAC name (4S)-4,11-Diethyl-4,9-dihydroxy-1,4-dihydro-3H,14H-pyrano[3′,4′:6,7]indolizino[1,2-b]quinoline-3,14-dione
Other names 7-Ethyl-10-hydroxycamptothecin
Identifiers
CAS Number	86639-52-3  N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:8988  N
ChEMBL	ChEMBL837  Y
ChemSpider	94634  Y
ECHA InfoCard	100.171.154
IUPHAR/BPS	6925
PubChem CID	104842
UNII	0H43101T0J  Y
CompTox Dashboard (EPA)	DTXSID4040399
InChI InChI=1S/C22H20N2O5/c1-3-12-13-7-11(25)5-6-17(13)23-19-14(12)9-24-18(19)8-16-15(20(24)26)10-29-21(27)22(16,28)4-2/h5-8,25,28H,3-4,9-10H2,1-2H3/t22-/m0/s1 Y Key: FJHBVJOVLFPMQE-QFIPXVFZSA-N Y
SMILES O=C\1N4\C(=C/C2=C/1COC(=O)[C@]2(O)CC)c3nc5c(c(c3C4)CC)cc(O)cc5
Properties
Chemical formula	C22H20N2O5
Molar mass	392.411 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N  verify  (what is  YN ?) Infobox references

SN-38 is an antineoplastic drug. It is the active metabolite of irinotecan (an analog of camptothecin - a topoisomerase I inhibitor) but has 1000 times more activity than irinotecan itself. In vitro cytotoxicity assays show that the potency of SN-38 relative to irinotecan varies from 2- to 2000-fold. ^[1]

SN38 is formed via hydrolysis of irinotecan by carboxylesterases and metabolized via glucuronidation by UGT1A1.

The variant of UGT1A1 in ~10% of Caucasians which leads to poor metabolism of SN-38 predicts irinotecan toxicity, as it is then less easily excreted from the body in its SN-38 glucuronide form. ^[2]

SN-38 and its glucuronide are lost into the bile and intestines. It can cause the symptoms of diarrhoea and myelosuppression experienced by ~25% of the patients administered irinotecan.

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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|alt=Irinotecan Pathway edit]]

Irinotecan Pathway edit

1. The interactive pathway map can be edited at WikiPathways: "IrinotecanPathway_WP229".

See also

• NK012, a nanodevice formulation of SN-38
• Sacituzumab govitecan, an antibody-drug conjugate that uses SN-38 as the cytotoxic drug.

References

1. "CAMPTOSAR- irinotecan hydrochloride injection, solution Pharmacia & Upjohn Company LLC".
2. O'Dwyer PJ, Catalano RB (October 2006). "Uridine diphosphate glucuronosyltransferase (UGT) 1A1 and irinotecan: practical pharmacogenomics arrives in cancer therapy". J. Clin. Oncol. 24 (28): 4534–8. doi: 10.1200/JCO.2006.07.3031 . PMID   17008691. Archived from the original on 2013-04-15. Retrieved 2014-01-14.